异氟烷对糖尿病模型大鼠缺血再灌注肾损伤的保护作用及其机制

Protective effect and mechanism of isoflurane on diabetic rats with renal ischemia-reperfusion injury

目的研究异氟烷(Iso)对糖尿病模型大鼠肾缺血再灌注(I/R)损伤的保护作用及其机制。方法清洁级雄性健康SD大鼠24只,单次ip注射链佐星60 mg·kg^-1制备糖尿病大鼠模型,72 h后空腹血糖>16.7 mol·L^-1认为造模成功。糖尿病模型大鼠分为3组:假手术组,肾I/R损伤组,2%Iso预处理+肾I/R损伤组(大鼠置2%Iso麻醉箱中预处理30 min,再进行肾I/R损伤模型制备)。肾I/R损伤手术后24 h,检测肾功能指标尿素氮(BUN)和肌酐(Cr),HE染色观察肾组织病理变化,TUNEL染色评估肾小管上皮细胞凋亡,免疫组化检测肾组织中肿瘤坏死因子α(TNF-α)和核因子-кB(NF-кB)的表达。结果与假手术组相比,糖尿病模型大鼠肾I/R损伤组的BUN和Cr升高,肾小管上皮细胞坏死和凋亡程度明显升高(P<0.01);TNF-α和NF-кB表达显著增高(P<0.01)。Iso预处理后显著抑制了BUN和Cr的升高,降低肾小管上皮细胞坏死和凋亡程度(P<0.01),明显抑制TNF-α和NF-кB的表达(P<0.01)。结论Iso预处理对糖尿病模型大鼠肾I/R损伤有保护作用,其机制可能与抑制BUN,Cr,TNF-α和NF-кB表达及肾小管上皮细胞坏死和凋亡有关。

OBJECTIVE To study the protective effect and mechanism of isoflurane(Iso)on diabetic rats with renal ischemia-reperfusion(I/R)injury.METHODS Male Sprague Dawley rats were injected with streptozotocin 60 mg·kg^-1 to prepare the diabetic model.Diabetic model rats were divided into 3 groups:sham group,renal I/R injury group,and Iso pretreatment+renal I/R injury group(exposed to 2%Iso for 30 min).24 h After renal I/R injury operation,blood urea nitrogen(BUN),creatinine(Cr),pathological changes and renal tubular epithelial cell apoptosis were assessed,and the expressions of tumor necrosis factor-α(TNF-α)and NF-кB in renal tissue were detected by immunohistochemistry.RESULTS Compared with sham group,Bun,Cr and tubular epithelial cell necrosis and apoptosis in rats of renal I/R injury group were significantly increased(P<0.01),so did the expressions of TNF-αand NF-κB(P<0.01).Iso pretreatment significantly inhibited the increase in BUN and Cr,the necrosis and apoptosis of renal tubular epithelial cells,and the expressions of TNF-α and NF-κB(P<0.01).CONCLUSION Iso can protect the kidney from I/R injury in diabetic rats.The mechanism may be related to the inhibition of BUN,Cr,TNF-αand NF-кB expressions by Iso.